crossing96/oncoscreening huggingface dataset:
Effect of liver metastasis on the efficacy of immune checkpoint inhibitors in cancer patients: a systemic review and meta-analysis.	Liver metastasis is a frequent phenomenon in advanced tumor disease. Immune checkpoint inhibitors (ICIs) are a new class of therapeutics that can improve the prognosis of cancer patients. The purpose of this study is to elucidate the relationship between liver metastasis and survival outcomes of patients receiving ICIs treatment. We searched four main databases, including PubMed, EMBASE, Cochrane Library, and Web of Science. Overall survival (OS) and progression-free survival (PFS) were the survival outcomes of our concern. Hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the relationship between liver metastasis and OS/ PFS. Finally, 163 articles were included in the study. The pooled results showed that patients with liver metastasis receiving ICIs treatment had worse OS (HR=1.82, 95%CI:1.59-2.08) and PFS (HR=1.68, 95%CI:1.49-1.89) than patients without liver metastasis. The effect of liver metastasis on ICIs efficacy differed in different tumor types, and patients with urinary system tumors (renal cell carcinoma OS: HR=2.47, 95%CI:1.76-3.45; urothelial carcinoma OS: HR=2.37, 95%CI:2.03-2.76) had the worst prognosis, followed by patients with melanoma (OS: HR=2.04, 95%CI:1.68-2.49) or non-small cell lung cancer (OS: HR=1.81, 95%CI:1.72-1.91). ICIs efficacy in digestive system tumors (colorectal cancer OS: HR=1.35, 95%CI:1.07-1.71; gastric cancer/ esophagogastric cancer OS: HR=1.17, 95%CI:0.90-1.52) was less affected, and peritoneal metastasis and the number of metastases have a greater clinical significance than liver metastasis based on univariate data. For cancer patients receiving ICIs treatment, the occurrence of liver metastasis is associated with poor prognosis. Different cancer types and metastatic sites may hold a different prognostic effect on the efficacy of ICIs treatment in cancer patients.	bladder
Non-muscle-invasive Bladder Cancer: Side-by-Side Guideline Comparison.	Clinical guidelines from the European Association of Urology, American Urological Association, Society of Urologic Oncology, and National Comprehensive Cancer Network are some of the most frequently accessed publications. These guidelines are published at varying frequency and use different methods to formulate their recommendations. Many guidelines still rely on expert opinion in areas where there is a lack of data. To be well executed guidelines they need to involve comprehensive panels who are content experts and multispecialty. This article reviews the strengths and weaknesses of current guidelines for non-muscle-invasive bladder cancer and possible opportunities for future improvements. PATIENT SUMMARY: Quality recommendations in guidelines are critical to provide the most effective care for patients with non-muscle-invasive bladder cancer.	bladder
β-asarone inhibits the migration, invasion, and EMT of bladder cancer through activating ER stress.	BACKGROUND: β-asarone (β-as), a compound extracted from Acorus calamus, has been found to have anticancer effects on a variety of human cancers. However, the potential effect of β-as on bladder cancer (BCa) remains unknown. METHODS: After exposure to β-as, migration, invasion, and epithelial-mesenchymal transition (EMT) of BCa were determined by wound healing, transwell, and Western blot assays. Expression of proteins involved in the EMT and ER stress were explored by Western blot assays. Nude mouse xenograft model was served as the model system in vivo. RESULTS: The migration, invasion, and EMT of BCa were significantly inhibited after β-as treatment. Further experiments revealed that endoplasmic reticulum (ER) stress is involved in β-as-mediated metastasis inhibition. In addition, β-as significantly up-regulated activating transcription factor 6 (ATF6), a branch of ER stress, and promoted its Golgi cleavage and nuclear localization. ATF6 silencing attenuated β-as-mediated metastasis and EMT inhibition in BCa cells. CONCLUSION: Our data suggests that β-as inhibits migration, invasion, and EMT of BCa by activating the ATF6 branch of ER stress. Thus, β-as represents a potential candidate for BCa treatment.	bladder
Use of machine learning to predict bladder cancer survival outcomes: a systematic literature review.	INTRODUCTION: The objective of this systematic review is to summarize the use of machine learning (ML) in predicting overall survival (OS) in patients with bladder cancer. METHODS: Search terms for bladder cancer, ML algorithms, and mortality were used to identify studies in PubMed and Web of Science as of February 2022. Notable inclusion/exclusion criteria contained the inclusion of studies that utilized patient-level datasets and exclusion of primary gene expression-related dataset studies. Study quality and bias were assessed using the International Journal of Medical Informatics (IJMEDI) checklist. RESULTS: Of the 14 included studies, the most common algorithms were artificial neural networks (n = 8) and logistic regression (n = 4). Nine articles described missing data handling, with five articles removing patients with missing data entirely. With respect to feature selection, the most common sociodemographic variables were age (n = 9), gender (n = 9), and smoking status (n = 3), with clinical variables most commonly including tumor stage (n = 8), grade (n = 7), and lymph node involvement (n = 6). Most studies (n = 10) were of medium IJMEDI quality, with common areas of improvement being the descriptions of data preparation and deployment. CONCLUSIONS: ML holds promise for optimizing bladder cancer care through accurate OS predictions, but challenges related to data processing, feature selection, and data source quality must be resolved to develop robust models. While this review is limited by its inability to compare models across studies, this systematic review will inform decision-making by various stakeholders to improve understanding of ML-based OS prediction in bladder cancer and foster interpretability of future models.	bladder
A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study.	Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.	bladder
Impact of Variant Histology on Oncological Outcomes in Upper Tract Urothelial Carcinoma: Results From the ROBUUST Collaborative Group.	INTRODUCTION: Oncologic implications of variant histology (VH) have been extensively studied in bladder cancer; however, further investigation is needed in upper tract urothelial carcinoma (UTUC). Our study aims to evaluate the impact of VH on oncological outcomes in UTUC patients treated with radical nephroureterectomy (RNU). METHODS: A retrospective analysis was performed on patients who underwent a robotic or laparoscopic RNU for UTUC using the ROBUUST database, a multi-institutional collaborative including 17 centers worldwide. Logistic regression was used to assess the effect of VH on urothelial recurrence (bladder, contralateral upper tract), metastasis, and survival following RNU. RESULTS: A total of 687 patients were included in this study. Median (IQR) age was 71 (64-78) years and 470 (68%) had organ confined disease. VH was present in 70 (10.2%) patients. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 26.8%, 15.3%, and 11.8%, respectively. VH was associated with increased risk of metastasis (HR 4.3, P <.0001) and death (HR 2.0, P =.046). In multivariable analysis, VH was noted to be an independent risk factor for metastasis (HR 1.8, P =.03) but not for urothelial recurrence (HR 0.99, P =.97) or death (HR 1.4, P =.2). CONCLUSION: Variant histology can be found in 10% of patients with UTUC and is an independent risk factor for metastasis following RNU. Overall survival rates and the risk of urothelial recurrence in the bladder or contralateral kidney are not affected by the presence of VH.	bladder
Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells.	Urothelial cancer (UC) is a common malignancy and its development is associated with arsenic exposure. Around 25% of diagnosed UC cases are muscle invasive (MIUC) and are frequently associated with squamous differentiation. These patients commonly develop cisplatin (CIS) resistance and have poor prognosis. SOX2 expression is correlated to reduced overall and disease-free survival in UC. SOX2 drives malignant stemness and proliferation in UC cells and is associated with development of CIS resistance. Using quantitative proteomics, we identified that SOX2 was overexpressed in three arsenite (As(3+))-transformed UROtsa cell lines. We hypothesized that inhibition of SOX2 would reduce stemness and increase sensitivity to CIS in the As(3+)-transformed cells. Pevonedistat (PVD) is a neddylation inhibitor and is a potent inhibitor of SOX2. We treated non-transformed parent and As(3+)-transformed cells with PVD, CIS, or in combination and monitored cell growth, sphere forming abilities, apoptosis, and gene/protein expression. PVD treatment alone caused morphological changes, reduced cell growth, attenuated sphere formation, induced apoptosis, and elevated the expression of terminal differentiation markers. However, the combined treatment of PVD with CIS significantly elevated the expression of terminal differentiation markers and eventually led to more cell death than either solo treatment. Aside from a reduced proliferation rate, these effects were not seen in the parent. Further research is needed to explore the potential use of PVD with CIS as a differentiation therapy or alternative treatment for MIUC tumors that may have become resistant to CIS.	bladder
Low co-expression of PD-L1 and oncogenic receptor tyrosine kinases HER2 and cMET in urothelial carcinoma is associated with discordant expression between primary and metastatic sites.	OBJECTIVES: Novel regimens targeting immune checkpoints and the cMET or HER2 pathways are under investigation in metastatic urothelial carcinoma (mUC) though co-expression of these molecular targets has not been defined. We sought to characterize the protein co-expression rates of PD-L1, cMET and HER2 in primary and metastatic mUC lesions and agreement rates in paired biopsies. MATERIALS AND METHODS: We assessed PD-L1, cMET and HER2 protein expression by immunohistochemistry (IHC) in archival mUC samples identified from an institutional database (n = 143). Correlation of expression between primary and metastatic biopsies was performed in patients with available paired biopsies (n = 79). Protein expression levels by predefined thresholds were measured, and Cohen's kappa statistics (κ) were utilized to assess the agreement in expression between paired primary and metastatic samples. RESULTS: In primary tumors (n = 85), high expression of PD-L1, cMET, and HER2 was observed in 14.1%, 34.1%, and 12.9%, respectively. In metastatic samples (n = 143), high expression of PD-L1, cMET and HER2 was detected in 9.8%, 41.3%, and 9.8%, respectively. Expression agreement rates between paired specimens (n = 79) were PD-L1: 79.7% (κ = 0.09), cMET: 69.6% (κ = 0.35), HER2: 84.8% (κ = 0.17). High PD-L1/cMET co-expression was observed in only 5.1% (n = 4) of primary and 4.9% (n = 7) of metastatic specimens. High co-expression of PD-L1/HER2 occurred in 3.8% (n = 3) of primary samples and no metastatic samples. The overall co-expression agreement between paired samples was 55.7% (κ = 0.22) for PD-L1/cMET and 67.1% (κ = 0.06) for PD-L1/HER2, but agreement for high co-expression between paired samples was very low (2.5% for PD-L1/cMET and 0% for PD-L1/HER2). CONCLUSIONS: Tumor co-expression of high cMET or HER2 and PD-L1 is low in this cohort. Agreement of high co-expression between primary and metastatic sites is rare. Biomarker-based strategies used in selection of patients for contemporary trials testing combinations of immune checkpoint inhibitors with either cMET or HER2-targeted agents should account for discordant biomarker expression between primary and metastatic sites.	bladder
The role of malnutrition universal screening tool in predicting outcomes after radical cystectomy.	PURPOSE: The Malnutrition Universal Screening Tool integrates body mass index, unintentional weight loss and present illness to assess risk for malnutrition. The predictive role of 'MUST' among patients undergoing radical cystectomy is unknown. We investigated the role of 'MUST' in predicting postoperative outcomes and prognosis among patients after RC. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis of 291 patients who underwent radical cystectomy in 6 medical centers between 2015 and 2019. Patients were stratified to risk groups according to the 'MUST' score [low risk (n = 242) vs. medium-to-high risk (n = 49)]. Baseline characteristics were compared between groups. Endpoints were 30-day postoperative complications rate, cancer-specific-survival and overall survival. Kaplan-Meier curves and Cox-regression analyses were used to evaluate survival and identify predictors of outcomes. RESULTS: Median age of the study cohort was 69 years (IQR 63-74). Median duration of follow up for survivors was 33 months (IQR 20-43). Thirty-day major postoperative complications rate was 17%. Baseline characteristics were not different between the 'MUST' groups, and there was no difference in early post-operative complication rates. CSS and OS were significantly lower (p ≤ 0.02) in the medium-to-high-risk group ('MUST' score≥1) with estimated 3-year CSS and OS rates of 60% and 50% compared to 76% and 71% in the low-risk group, respectively. On multivariable analysis, 'MUST'≥1 was an independent predictor of overall- (HR = 1.95, p = 0.006) and cancer-specific-mortality (HR = 1.74, p = 0.05). CONCLUSIONS: High 'MUST' scores are associated with decreased survival in patients after radical cystectomy. Thus, the 'MUST' score may serve as a preoperative tool for patient selection and nutritional intervention.	bladder
[Antibody-drug conjugates as new therapeutic agents in uro-oncology].	"Antibody-drug conjugates represent a new class of therapeutic agents that are already being used in the field of uro-oncology. They consist of an antibody directed against a specific tumour antigen linked to a cytotoxic substance (""payload"") which acts after internalisation into the tumour cell and its release. Currently, approval in the European Union is restricted to enfortumab vedotin which is directed against nectin‑4 and carries the microtubule-inhibiting active ingredient monomethyl auristatin E (MMAE). Enfortumab vedotin is approved for locally advanced or metastatic urothelial carcinoma in the third line of therapy after platinum-based chemotherapy and after therapy with a programmed cell death (ligand) 1 (PD-[L]1) immune checkpoint inhibitor. However, an expansion of the indication of enfortumab vedotin as monotherapy and in combination with PD-(L)1 immune checkpoint inhibitors, as well as approval of other antibody-drug conjugates is expected in the future. This could sustainably change the therapy sequence in urothelial carcinoma. Currently, several clinical trials are recruiting in different therapeutic settings. This article presents the new substance class of antibody-drug conjugates, their mechanism of action, their representatives and clinical studies, and points out practice-relevant side effects and how to deal with them."	bladder
Utility and performance of cell blocks in urine cytology: Experience at three teaching hospitals.	BACKGROUND: The use of cell block (CB) preparation is underused in urine cytology (UC) and varies among hospitals. In addition to confirming a diagnosis, CBs can be useful in cases of metastatic disease, diagnoses requiring immunohistochemical (IHC) staining, and for ancillary studies. The role of this study is to examine the performance of CBs for UC at three affiliated teaching hospitals. MATERIALS AND METHODS: A retrospective review of UC cases with a CB was conducted at a county hospital, Veterans Affairs hospital, and tertiary university-based hospital. For each specimen, patient demographics, specimen type, volume, original diagnosis, and IHC stains were recorded. Each case was reviewed for diagnosis based on ThinPrep alone, diagnosis based on ThinPrep and CB, utility of CB for diagnosis, and CB cellularity. RESULTS: A total of 250 UC specimens with CB from 186 patients was identified. Bladder washes were the most common (72.1%). IHC stains were performed on 17.2% of cases. On blinded review, CB preparation was deemed useful in 61.2% of cases, with the highest rate for suspicious for high-grade urothelial carcinoma (SHGUC) cases (87.0%). The diagnosis based on ThinPrep review changed with incorporation of CB in 13.2% of cases, with the highest rate for SHGUC cases (43.5%). CONCLUSIONS: The results demonstrate that use of CB in UC confirms the final diagnosis in more than one-half of cases and changes the diagnosis in a subset of cases. Use of CB was most helpful in the SHGUC category. Further evaluation of the types of cases in which CB are prepared is warranted.	bladder
Real-world retrospective study of immune checkpoint inhibitors in combination with radiotherapy or chemoradiotherapy as a bladder-sparing treatment strategy for muscle-invasive bladder urothelial cancer.	BACKGROUND: Recent developments in MIBC treatment suggest good efficacy of bladder sparing treatment combined with immune checkpoint inhibitor. However, there is no standard treatment mode. A retrospective analysis was conducted to reveal the efficacy and safety of PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy. METHODS: We retrospectively analyzed 25 patients with MIBC T2-T3N0M0 disease who were unfit or unwilling to undergo RC. These patients underwent the maximum TURBT followed by PD-1 inhibitor (Tislelizumab or Toripalimab) in combination with radiotherapy or chemoradiotherapy (gemcitabine plus cisplatin) between April 2020 and May 2022. The primary outcome was clinical complete response (cCR) rate. The secondary outcomes were disease free survival (DFS) and overall survival (OS). RESULTS: Revised: Of 25 patients, 22 were T2 (88%), while 3 were T3 (12%). The median age is 65 years (51-80). Twenty-one patients had programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or more, and 4 patients had CPS<1 or unknown. Sixteen patients received chemoradiotherapy. Tislelizumab and Toripalimab were administered to 19 and 6 patients, respectively. The median number of cycles of immunotherapy was 8. Twenty-three patients (92%) achieved cCR. Following a median of 13 months of follow-up (range, 5-34 months), 1-year DFS and OS rate were 92% and 96%, respectively. In the univariate analysis, T stage significantly influenced OS and ORR, and efficacy evaluation significantly influenced OS, DFS, and ORR. The expression of PD-L1 and chemotherapy had no effect on prognosis. In the multivariate analysis, no independent prognostic factors were found. Grade 3 or 4 adverse events (AE) were reported in 35.7% patients. CONCLUSIONS: Bladder sparing therapy with PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy is feasible, safe, and highly effective for patients who were unfit or unwilling to undergo RC.	bladder
Optimizing outcomes and managing adverse events in locally advanced or metastatic urothelial cancer: a clinical pharmacology perspective.	INTRODUCTION: Bladder cancer (BC) is the sixth most common type of cancer with epithelial/urothelial and non-urothelial origins. Urothelial carcinoma (UC) involves neoplastic cells of epithelial origin and accounts for 90% of all BC cases. Current review aims to discuss the latest advances and challenges in the treatment of UC with an emphasis on clinical pharmacology considerations. AREAS COVERED: Data including clinical efficacy and safety outcomes as well as precautions reported in published clinical studies obtained from PubMed and package inserts were collected and summarized in the review. Recent decade saw the approval of multiple drugs for the treatment of BC in both adjuvant/neoadjuvant setting as well as for unresectable tumors. Checkpoint blockers (pembrolizumab, nivolumab, atezolizumab, and avelumab), antibody drug conjugates (enfortumab vedotin and sacituzumab govitecan) and targeted therapies (erdafitinib) are now available in first-line (cisplatin-ineligible), second-line and third-line settings along with conventional platinum-based chemotherapy. While the survival outcomes have improved especially in refractory and unresponsive patients, the response rates are relatively low and patient safety needs further optimization. EXPERT OPINION: Additional studies on combination therapies, dose adjustments in special populations and impact of anti-drug antibodies on drug exposure are needed to further improve clinical outcomes.	bladder